Despite decades of research, the development of a successful HIV-1 vaccine has not yet been achieved. A better understanding of the functions of activated lymphocytes is therefore desired. The long-term objective of our research is to comprehend the full potentials of HIV-1-envelope-specific immune cells. CD4+ T-cells contribute to HIV-1 control by supporting antibody production by 8-cells and the activation/maintenance of CD8+ T-cells. However, based on our recent data, it appears that envelope-specific CD4+ T-cells may additionally contribute directly to the control of virus-infected cells, independent of 8-cell or CD8+ T-cell activity. The studies proposed here will determine how these CD4+ T-cells confer their 'protector' effect. Specific Aim: To determine the phenotype, cytokine secretion capacities, and killer potentials of the HIV-1 envelope-specific CD4+ T-cells that protect against envelope-recombinant virus in the absence of 8-cell or CD8+ T-cell functions. Experiments are designed to fill fundamental gaps in our understanding of how virus is controlled by the immune system. Results from these experiments may be invaluable to the construction of new, successful HIV-1 vaccines designed to capture the full potentials of the immune response.